Recent Advances in Self-Exciting Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is already (Food and Drug Administration) FDA approved and used in the clinic for oncological treatment of pancreatic, lung, esophagus, bile duct, and of course several cancers of skin. It is an important tool in the oncological array of treatments, but for it exist several shortcomings, the most prominent of which is the shallow depth penetration of light within tissues. One-way researchers have attempted to circumvent this is through the creation of self-exciting "auto-PDT" nanoplatforms, which do not require the presence of an external light source to drive the PDT process. Instead, these platforms are driven either through oxidative chemical excitation in the form of chemiluminescence or radiological excitation from beta-emitting isotopes in the form of Cherenkov luminescence. In both, electronic excitations are generated and then transferred to the photosensitizer (PS) via Resonance Energy Transfer (RET) or Cherenkov Radiation Energy Transfer (CRET). Self-driven PDT has many components, so in this review, using contemporary examples from literature, we will breakdown the important concepts, strategies, and rationale behind the design of these self-propagating PDT nanoplatforms and critically review the aspects which make them successful and different from conventional PDT. Particular focus is given to the mechanisms of excitation and the different methods of transfer of excited electronic energy to the photosensitizer as well as the resulting therapeutic effect. The papers reviewed herein will be critiqued for their apparent therapeutic efficiency, and a basic rationale will be developed for what qualities are necessary to constitute an "effective" auto-PDT platform. This review will take a biomaterial engineering approach to the review of the auto-PDT platforms and the intended audience includes researchers in the field looking for a new perspective on PDT nanoplatforms as well as other material scientists and engineers looking to understand the mechanisms and relations between different parts of the complex "auto-PDT" system.

Photodynamic Therapy—Current Limitations and Novel Approaches

“…Alternative routes can be utilized in order to overcome depth limitations in addition to the use of external excitation sources. In addition to these studies, the auto-PDT strategy, which aims to increase PDT efficiency without requiring the presence of an external light source, has also been utilized ( Blum et al, 2020 ). A self-illuminating nanoparticle was designed as a PDT agent which can be excited by enzyme-mediated bioluminescence approaches ( Fan et al, 2016 ; Ozdemir et al, 2017 ).…”

Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer

“…Designing of PS-radioisotope conjugates or NPs requires careful consideration of the type of radionuclide and radiolabeling strategy, high in vivo stability and potential long-term toxicity. Another importance of employing radiolabelled (β-emitters) PS conjugates or NPs, is in Cherenkov Radiation Energy Transfer for exciting PS deep in the tissue without the application of an external light source as self-exciting “auto-PDT” 188 . Radiolabeled PSs are useful for localizing the biodistribution of PS mainly in the tumor mass and for PS uptake studies; however, they cannot be used for visualization of post-PDT effects due to the loss of PS selectivity and uptake by tumor tissue.…”

Recent Advances in Photodynamic Therapy for Deep-Seated Tumors with the Aid of Nanomedicine

“…Another strategy to overcome light penetration in PDT is through the creation of self-exciting nanoplatforms, which do not need an external light source for PS activation. These platforms are driven either from a specific chemical reaction or enzyme catalytic biochemical reaction in a tumor [ 38 ]. Wu et al formulated a chemiluminescence resonance energy transfer (CRET) strategy for solid tumor PDT by using a nanoreactor in which the NP encapsulated bis[3,4,6-trichloro-2-(pentyloxycarbonyl) phenyl] oxalate (CPPO), poly[(9,9’-dioctyl-2,7-divinylene-fluorenylene)-alt-2-methoxy5-(2-ethyl-hexyloxy)-1,4-phenylene] (PFPV) and the tetraphenylporphyrin (TPP) as a PS.…”